Document Detail


First clinical application of an actively reversible direct factor IXa inhibitor as an anticoagulation strategy in patients undergoing percutaneous coronary intervention.
MedLine Citation:
PMID:  20660806     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The ideal anticoagulant should prevent ischemic complications without increasing the risk of bleeding. Controlled anticoagulation is possible with the REG1 system, an RNA aptamer pair comprising the direct factor IXa inhibitor RB006 and its active control agent RB007. METHODS AND RESULTS: This phase 2a study included a roll-in group (n=2) treated with REG1 plus glycoprotein IIb/IIIa inhibitors followed by 2 groups randomized 5:1 to REG1 or unfractionated heparin. In group 1 (n=12), RB006 was partially reversed with RB007 after percutaneous coronary intervention and fully reversed 4 hours later. In group 2 (n=12), RB006 was fully reversed with RB007 immediately after percutaneous coronary intervention. Femoral sheaths were removed after complete reversal. Patients were pretreated with aspirin and clopidogrel. End points included major bleeding within 48 hours; composite of death, myocardial infarction, or urgent target vessel revascularization within 14 days; and pharmacodynamic measures. All cases were successful, with final Thrombolysis in Myocardial Infarction grade 3 flow and no angiographic thrombotic complications. There were 2 ischemic end points in the REG1 group and 1 in the unfractionated heparin group, with 1 major bleed in the unfractionated heparin group. Median activated clotting time values rose from 151 to 236 seconds after RB006. Administration of the partial RB007 dose reversed anticoagulation to an intermediate activated clotting time value of 186 seconds. Complete reversal with RB007 returned the median activated clotting time value to 144 seconds. Both reversal strategies enabled scheduled femoral sheath removal. CONCLUSIONS: This study demonstrates the clinical translation of a novel platform of anticoagulation targeting factor IXa and its active reversal to percutaneous coronary intervention and provides the basis for further investigation. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00715455.
Authors:
Mauricio G Cohen; Drew A Purdy; Joseph S Rossi; Liliana R Grinfeld; Shelley K Myles; Laura H Aberle; Adam B Greenbaum; Edward Fry; Mark Y Chan; Ross M Tonkens; Steven Zelenkofske; John H Alexander; Robert A Harrington; Christopher P Rusconi; Richard C Becker
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Publication Detail:
Type:  Clinical Trial, Phase II; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-07-26
Journal Detail:
Title:  Circulation     Volume:  122     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-10     Completed Date:  2010-08-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  614-22     Citation Subset:  AIM; IM    
Affiliation:
Cardiovascular Division, University of Miami Miller School of Medicine, Miami, FL 33136, USA. mgcohen@med.miami.edu
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00715455
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MeSH Terms
Descriptor/Qualifier:
Aged
Angioplasty, Transluminal, Percutaneous Coronary* / adverse effects,  methods
Anticoagulants / adverse effects,  pharmacology,  therapeutic use*
Aptamers, Nucleotide / adverse effects,  therapeutic use
Coronary Disease / blood,  drug therapy*,  therapy
Factor IXa / antagonists & inhibitors*,  metabolism
Feasibility Studies
Female
Heparin / adverse effects,  analogs & derivatives,  therapeutic use
Humans
Male
Middle Aged
Oligonucleotides / adverse effects,  therapeutic use
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Aptamers, Nucleotide; 0/Oligonucleotides; 0/RB 006; 0/RB 007; 129480-74-6/ITF 300; 9005-49-6/Heparin; EC 3.4.21.22/Factor IXa

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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